Chiesi's rare disease strategy expands into genetic medicines with partnership with CRISPR startup Arbor
In the five years since Italy's Chiesi Group launched its rare diseases unit in Boston, 10 of its therapies have won regulatory approval around the world — all small molecules and engineered proteins. Recently, the company has been exploring ways to expand its product portfolio in ways that can have a greater, longer-lasting impact on patients. The next step in the strategy is to take the company into the field of genetic medicines.
Giacomo Chiesi, executive vice president of Chiesi's global rare diseases unit, said Chiesi's global rare diseases unit has been focusing on oral small molecule drugs and enzyme replacement therapies because these drugs are the types of drugs the company is familiar with. But he added that growth required new models of which the sector had no experience. The company is now adding CRISPR-based gene editing to its toolbox, announcing this week a $115 million commitment to a partnership with Arbor Biotechnologies, based near Cambridge, Massachusetts. The deal brings a clinical-stage rare disease therapy and the platform technology to create it.
“We feel like we're a little behind in bringing treatments to patients,” Chiesi told MedCity News. “So, from our perspective, this is another important tool in a series of solutions that we want to bring to patients in a clear way in the future.”
The core asset of the transaction is Arbor's asset ABO-101, a gene-editing therapy for primary hyperoxaluria type 1 (PH1). This genetic rare disease starts in the liver but manifests as kidney problems. People with PH1 lack the enzyme needed to break down oxalate, a compound produced by the liver. As a result, oxalates accumulate in the kidneys, forming kidney stones and damaging the organ, explains Arbor CEO Devyn Smith. PH1 can lead to end-stage renal disease, which requires organ transplantation—a temporary solution. Since the root of the disease is in the liver, the new kidneys are unable to resolve the excess oxalates in the body, so the transplanted organ eventually becomes damaged.
Current FDA-approved treatments for PH1 use small interfering RNA to block the production of an enzyme key to oxalate production. These genetic drugs do lower oxalate levels, but they are chronic treatments — Alnylam Pharmaceuticals' Oxlumo is an injection every three months, while Novo Nordisk's Rivfloza is a monthly injection. Arbor's ABO-101 is a potential one-time treatment. It also goes beyond current gene-editing methods.
CRISPR first reaches patients as an ex vivo therapy, in which the editing is done in the laboratory and the genetically engineered cells are infused back into the patient. Arbor's ABO-101 edits in the patient's body. Its genetic material is encapsulated within lipid nanoparticles, a type of particle that targets the liver. This Arbor therapy targets the same enzyme as Alnylam and Novo Nordisk's PH1 drug, but uses CRISPR to knock out the gene encoding the enzyme. Smith acknowledged the availability of chronic PH1 therapies, but said ABO-101 offers PH1 patients a chance to escape the disease.
“If you think about the one-and-done approach as a parent, if my child has a chronic disease, I would rather have that disease go away so they can live their lives and do the things they need to do and not have to carry the burden of that disease for the rest of their lives,” he said.
Chiesi said that in addition to the potential long-term durability of Arbor's therapy, his company also hopes to create a better treatment experience for patients. The first generation of gene-editing drugs required a conditioning regimen to prepare the patient's body for treatment. This treatment uses toxic drugs, which can be difficult for patients, especially children. Because Arbor's therapy edits within the patient's body, no pretreatment is required.
Biotechs developing in vivo gene editing therapies include Editas Medicines, Intellia Therapeutics, Mammoth Biosciences, Precision Biosciences and Scribe Therapeutics. All of these companies already have partners. Arbor also has partners, although those agreements are for ex vivo therapies. Chiesi said his company spoke with several gene-editing biotech companies with projects in various stages of development and selected Arbor after an 18-month due diligence process.
Arbor did not initially plan to work with its most advanced program, the ABO-101, Smith said. Earlier this year, Arbor completed a $73.9 million Series C round of financing to support the clinical development of its PH1 program. But he added that as a startup with platform technology, Arbor continues to receive inquiries about its technology and pipeline. Smith said the partnership with Chiesi Global Rare Medicines puts ABO-101 into the hands of a company that is committed to rare disease research and brings knowledge and experience in the field. With development of ABO-101 now led by partners, Arbor can focus on bringing in vivo gene editing to other indications beyond the liver. Arbor's development pipeline includes three preclinical programs, each targeting a different target in amyotrophic lateral sclerosis (ALS).
Chiesi Global Rare Disease Company is launching the Arbor Alliance and providing up to $115 million in upfront and near-term payments to its partners. The gene-editing company could receive up to $2 billion in milestone payments and royalties on sales of approved products from the study.
ABO-101 began a Phase 1/2 clinical trial this summer; the target enrollment is 23 patients. Chiesi said Arbor remains a sponsor of the trial, but Chiesi Global Rare Diseases will collaborate on the study and will lead future clinical testing of the therapy. The agreement also grants the rare disease company the option to use Arbor's gene editing platform to develop novel liver-targeted therapies for rare diseases. Chiesi said the targets were predetermined but not yet made public. The two private companies also did not reveal a timetable for the release of the ABO-101 study, but Chiesi said clinical trials and broader partnerships are proceeding with urgency.
“Patients can’t wait for new solutions – and that’s driving growth for both organizations,” he said. “As a result, we will be fast and efficient in future clinical development.”
Illustration: libre de droit via Getty Images
